The overall objective of this project is to understand the mechanisms of leukemogenesis. The proposed studies are designed to increase our knowledge about the role of oncogene expression in initiating and maintaining transformation of myeloid leukemia cells. The human homologues of the viral oncogenes of acutely transforming retroviruses have been implicated in the pathogenesis of human leukemias, for example, c-abl, the human homologue of the oncogene of Abelson murine leukemia virus, is translocated in Philadelphia chromosome positive chronic myelogenous leukemia. Understanding leukemic transformation by viral oncogenes can suggest the possible role of their human homologues in human leukemogenesis. This study proposes to determine the role of v abl, the viral oncogene of Abelson murine leukemia virus, in initiating and maintaining transformation of Abelson virus infected murine myeloid cells. Leukemic transformation has been defined as acquisition of the capacity for progressive growth in vivo. Using a system which will allow sequential analysis of the phenotypic characteristics, growth factor requirements, and leukemogenicity of infected cells, it will be determined if v-abl expression is sufficient for transformation of myeloid cells, and if transformation is a temporally discrete event correlated with v-abl expression, or if it is the result of a multistage process, perhaps requiring additional alterations of cellular genes. Promonocytic leukemia cell lines isolated from Abelson virus infected mice will be used to determine the relationship between v abl expression and the capacity for terminal differentiation in transformed cells. Additionally, both established leukemia lines and newly infected cells will be used to investigate the association of v-abl expression with autocrine production of myeloid cell growth factors. These studies are designed to test the hypothesis that expression of the Abelson virus oncogene is not sufficient for transformation of myeloid cells, and that Abelson virus oncogene expression in myeloid cells is associated with autocrine secretion of specific hemopoietic growth regulatory factors.